Ascertainment of uninterrupted CAG repeat length and disease-modifying variants in fragment-based genetic testing for Huntington Disease.

ABSTRACT:

Purpose

In Huntington disease (HD), synonymous variants causing loss or duplication of the interrupting CAA codon in the HTT CAG repeat modify disease onset. These variants are undetectable during HD genetic testing, resulting in inaccurate diagnostic reporting of uninterrupted CAG repeat length. Inaccurate reporting of CAG repeat length results in misdiagnosis of individuals with alleles near diagnostic cut-offs. We present a method to identify variant alleles during CAG repeat genotyping, allowing accurate diagnostic reporting of uninterrupted CAG repeat length.

Methods

We used triplet-primed PCR (TP-PCR) to amplify HTT CAG repeat alleles with canonical or noncanonical repeat interruptions and leveraged differences in peak amplification patterns to develop a

SUBMITTER: Findlay Black H 

PROVIDER: S-EPMC11613659 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature